The theme of this program project is to define and quantitate the effects of certain cigarette smoke constituents, some of which are broadly distributed in nature in other plant products, on the immune system broadly defined to include humoral and cellular immunity (Projects I, III, and V), coagulation pathways (Projects I and II), the complement system (Projects II and IV), and how these, acting individually or in concert, may contribute to arteriosclerosis (Projects I and III), thrombosis and ischemic injury (Project II) and cardiac arrhythmia and sudden death (Project V). We also propose to determine if the effects of cigarette smoking on these pathways contributes to the pathogenesis of utero-placental injury and are the basis of the association between cigarette smoking and perinatal morbidity and mortality (Project II). Through the studies proposed we hope to gain a better understanding of the multiple mechanisms by which cigarette smoking can perturb the immune system. This may provide insight into its association with cardiovascular, pulmonary, and perinatal disease, insight into the nature of other unidentified exogenous risk factors in the diet or the work place which might work through similar immunopathologic mechanisms, and a mechanistic and clinically measurable definition of those individuals who are at risk. Titles of component research projects are as follows: Project I - Anti-idiotypic Responses and Cardiovascular Disease. Project II - Experimental Cardiac and Uteroplacental Injury in Rabbits. Project III - Immunobiology of Tobacco and Related Plant Products. Project IV - Tobacco, Plant Products and the Complement System. Project V - Cardiovascular and Pulmonary Immune Responses to Tobacco.